The broad aim of this proposal is to enlarge our knowledge of the role of the lipid moieties of membrane lipoproteins in physiological events mediated by biological membranes. The proposed research concentrates on the elucidation of the dynamic functions of membrane phospholipids in selected systems or under circumstances judged capable of providing new information which will contribute to the eventual understanding of specific roles of these substances. The research design comprises four areas of investigation each of which is a continuation or logical extension of ongoing work: 1) Additional studies will be conducted on the subcellular and intralaminar distribution and metabolism of brain polyphosphoinositides, with emphasis on the portion associated with non-myelin structures. 2) The stimulatory effects of pharmacological agents, especially neurotransmitters, beta-adrenergic receptor blocking agents and local anesthetics, on phospholipid metabolism in the isolated rat pineal gland will be further examined. The goal of this project is to shed light on the control of phospholipid metabolic pathways and to gain information as to the mode of action of the drugs used. 3) The metabolism of the fatty acid moieties of cardiolipin will continue to be investigated with the aim of characterization of the enzymatic reactions which acylate and deacylate this phospholipid. 4) An investigation will be undertaken of the lipid composition and metabolism in cloned lines of a cultured mouse neuroblastoma. The changes in phospholipid metabolism which may occur when cells are either incubated in the presence of drugs which act on the central nervous system or grown under conditions which induce the differentiation of processes will be particularly explored. Basic knowledge acquired as a result of these studies may help to reveal the subtle changes which likely occur in membranes in both normal and disease processes.